入院时和随访期间血清钙卫蛋白水平预测 COVID-19 患者的严重程度和结局：一项前瞻性研究。
Calprotectin serum levels on admission and during follow-up predict severity and outcome of patients with COVID-19: A prospective study.
机构信息
Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa, Greece; European Reference Network on Hepatological Diseases (ERN RARE-LIVER), General University Hospital of Larissa, Larissa, Greece.
Research and Development, Headquarters & Technology Center Autoimmunity, Werfen, San Diego, CA 92131, USA.
出版信息
Eur J Intern Med. 2024 Apr;122:78-85. doi: 10.1016/j.ejim.2023.11.001. Epub 2023 Nov 11.
BACKGROUND & AIMS: Calprotectin reflects neutrophil activation and is increased in various inflammatory conditions including severe COVID-19. However, serial serum calprotectin measurements in COVID-19 patients are limited. We assessed prospectively, calprotectin levels as biomarker of severity/outcome of the disease and a COVID-19 monitoring parameter in a large cohort of consecutive COVID-19 patients.
METHODS
Calprotectin serum levels were measured in 736 patients (58.2 % males; median age 63-years; moderate disease, n = 292; severe, n = 444, intubated and/or died, n = 50). Patients were treated with combined immunotherapies according to our published local algorithm. The endpoint was the composite event of intubation due to severe respiratory failure (SRF)/COVID-19-related mortality.
RESULTS
Median (interquartile range) calprotectin levels were significantly higher in patients with severe disease [7(8.2) vs. 6.1(8.1)μg/mL, p = 0.015]. Calprotectin on admission was the only independent risk factor for intubation/death (HR=1.473, 95 %CI=1.003-2.165, p = 0.048) even after adjustment for age, sex, body mass index, comorbidities, neutrophils, lymphocytes, neutrophil to lymphocytes ratio, ferritin, and CRP. The area under the curve (AUC, 95 %CI) of calprotectin for prediction of intubation/death was 0.619 (0.531-0.708), with an optimal cut-off at 13 μg/mL (sensitivity: 44 %, specificity: 79 %, positive and negative predictive values: 13 % and 95 %, respectively). For intubated/died patients, paired comparisons from baseline to middle of hospitalization and subsequently to intubation/death showed significant increase of calprotectin (p = 0.009 and p < 0.001, respectively). Calprotectin alteration had the higher predictive ability for intubation/death [AUC (95 %CI):0.803 (0.664-0.943), p < 0.001].
CONCLUSIONS
Calprotectin levels on admission and their subsequent dynamic alterations could serve as indicator of COVID-19 severity and predict the occurrence of SRF and mortality.
背景与目的
钙卫蛋白反映中性粒细胞的激活，在包括严重 COVID-19 在内的各种炎症情况下增加。然而，对 COVID-19 患者的血清钙卫蛋白进行连续测量的研究有限。我们前瞻性评估了钙卫蛋白水平作为疾病严重程度/结局的生物标志物，以及 COVID-19 监测参数在一组连续 COVID-19 患者中的作用。
方法
我们测量了 736 名患者（58.2%为男性；中位年龄 63 岁；中度疾病患者 292 例；严重疾病患者 444 例，需要插管和/或死亡的患者 50 例）的血清钙卫蛋白水平。患者根据我们发表的当地算法接受联合免疫治疗。终点是严重呼吸衰竭（SRF）/COVID-19 相关死亡率导致的插管复合事件。
结果
严重疾病患者的中位（四分位距）钙卫蛋白水平显著较高[7（8.2）μg/mL 比 6.1（8.1）μg/mL，p=0.015]。入院时的钙卫蛋白是插管/死亡的唯一独立危险因素（HR=1.473，95%CI=1.003-2.165，p=0.048），即使在调整年龄、性别、体重指数、合并症、中性粒细胞、淋巴细胞、中性粒细胞与淋巴细胞比值、铁蛋白和 CRP 后也是如此。钙卫蛋白预测插管/死亡的曲线下面积（AUC，95%CI）为 0.619（0.531-0.708），最佳截断值为 13μg/mL（灵敏度：44%，特异性：79%，阳性和阴性预测值分别为 13%和 95%）。对于插管/死亡患者，从基线到住院中期以及随后到插管/死亡的配对比较显示钙卫蛋白显著增加（p=0.009 和 p<0.001）。钙卫蛋白的变化对插管/死亡具有更高的预测能力[AUC（95%CI）：0.803（0.664-0.943），p<0.001]。
结论
入院时的钙卫蛋白水平及其随后的动态变化可作为 COVID-19 严重程度的指标，并预测 SRF 和死亡率的发生。
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